Fatty Acid Metabolism

Question 1

Why are triacylglycerols great energy stores?

Answer 1

1. They are highly reduced. Oxidation yields ~38 kJ/g (vs. 17 kJ/g for carbohydrates)
2. They are nearly anhydrous, stored in virtually water-free droplets vs. 2 kJ/g for glycogen

All together, this results in ~6x more energy than glycogen for each gram of fat

Question 2

What are the steps of fatty acid utilization?

Answer 2

1. Mobilization: adipose tissue –> energy-requiring tissue
2. Activation/transport: into mitochondria for degradation
3. β-oxidation: stepwise breakdown to acetyl-CoA

Question 3

How are fatty acids mobilized?

Answer 3

adipose tissue –> bloodstream

• lipolysis by hormones such as epinephrine and glucagon
• via G_s to stimulate triacylglycerol release
• hormone-sensitive lipase yields free fatty acids
• released into blood stream!

Question 4

How are fatty acids carried into the tissues they need to reach?

Answer 4

serum albumin

They bind serum albumin which can bind up to 10 fatty acids per molecule and act as a carrier for their transport

Question 5

Where does fatty acid oxidation take place?

Answer 5

mitochondrial matrix (like the TCA cycle)

Question 6

How are fatty acids activated and when?

Answer 6

• fatty acyl-CoA synthetase (standard free energy = -34 kJ/mol)
• fatty acid attacks ATP, generating AMP and PP_i
• CoA-SH attacks the carbonyl and AMP comes off, leaving fatty acyl-CoA

Question 7

How oes fatty acyl-CoA get across the inner mitochonrial membrane?

Answer 7

The carnitine shuttle

1. carnitine acyltransferase I replaces CoA with carnitine
2. transporter shuttles fatty acyl-carnitine across inner membrane into matrix
3. regenerate fatty acyl-CoA and carnitine using carnitine acyltransferase II
4. carnitine returned to intermembrane space in exchange for fatty acyl-carnitine

Question 8

What are the steps of β-oxidation?

Answer 8

Saturated fatty acyl-CoA degraded by four reactions:

1. oxidation by FAD
2. hydration
3. oxidation by NAD⁺
4. thiolysis

chain shortene by two carbons, generate FADH₂, NADH, acetyl-CoA

Question 9

What happens in fatty acid catabolism for fatty acids with an odd number of carbons?

Answer 9

Additional steps are required.

One succinyl-CoA is yielded via propionyl-CoA

Question 10

When are additional steps required for fatty acid catabolism?

Answer 10

• double bonds (unsaturated fatty acids)
• odd number of carbones
• branced fatty acids

Question 11

What is necessary for the breakdown of unsaturated fatty acids?

Answer 11

isomerase and sometimes reductase

Question 12

What is the net ATP yield for breakdown of palmitoyl-CoA?

Answer 12

108.

Know how to do this calculation.

Question 13

What happens at the end of one round of β-oxidation?

Answer 13

The shortened acyl-CoA undergoes another round…

Question 14

What are the products of β-oxidation?

Answer 14

• fatty acyl-CoA, two carbons shorter than at the start
• acetyl-CoA

Question 15

Where does fatty acid synthesis take place?

Answer 15

The cytosol

Question 16

What are intermediates attached to during fatty acid synthesis?

Answer 16

acyl carrier protein

Question 17

What are intermediates attached to during fatty acid breakdown?

Answer 17

CoA

Question 18

What is the reductant in fatty acid synthesis?

Answer 18

NADPH

Question 19

What are the oxidants in fatty acid degradation?

Answer 19

NAD+ and FADH₂

Question 20

How is malonyl-CoA synthesized?

Answer 20

From acetyl-CoA and bicarbonate by acetyl-CoA carboxylase with the use of biotin

Question 21

What drives the process of fatty acid synthesis?

Answer 21

decarboxylation of malonyl-CoA which allows the remaining two carbons to attach to the acetyl group

Question 22

What does each round of fatty acid synthesis consume?

Answer 22

one malonyl-CoA, two NADPH, releases one CO₂

Question 23

When does fatty acid synthesis stop?

Answer 23

With palmitate

Question 24

Where does NADPH come from for fatty acid synthesis?

Answer 24

pentose phosphate pathway

converting malate to pyruvate with malic enzyme